Left Ventricular Wall Thickness Research Articles

Chronic kidney disease activates the HDAC6-inflammatory axis in the heart and contributes to myocardial remodeling in mice: inhibition of HDAC6 alleviates chronic kidney disease-induced myocardial remodeling.

Chronic kidney disease (CKD) adversely affects the heart. The underlying mechanism and the interplay between the kidney and the heart are still obscure. We examined the cardiac effect using the unilateral ureteral obstruction (UUO)-induced CKD pre-clinical model in mice. Echocardiography, histopathology of the heart, myocardial mRNA expression of ANP and BNP, the extent of fibrotic (TGF-β, α-SMA, and collagen I) and epigenetic (histone deacetylases, namely HDAC3, HDAC4, and HDAC6) proteins, and myocardial inflammatory response were assessed. Six weeks of post-UUO surgery, we observed a compromised left-ventricular wall thickness and signs of cardiac hypertrophy, accumulation of fibrosis associated, and inflammatory proteins in the heart. In addition, we observed a perturbation of epigenetic proteins, especially HDAC3, HDAC4, and HDAC6, in the heart. Pharmacological inhibition of HDAC6 using ricolinostat (RIC) lessened cardiac damage and improved left-ventricular wall thickness. The RIC treatment substantially restored the serum cardiac injury markers, namely creatine kinase-MB and lactate dehydrogenase (LDH) activities, ANP and BNP mRNA expression, and heart histological changes. The extent of myocardial fibrotic proteins, phospho-NF-κB (p65), and pro-inflammatory cytokines (TNF-α, IL-18, and IL-1β) were significantly decreased in the RIC treatment group. Further findings revealed the CKD-induced infiltration of CD3, CD8a, CD11c, and F4/80 positive inflammatory cells in the heart. Treatment with RIC substantially reduced the myocardial infiltration of these inflammatory cells. From these findings, we believe that CKD-induced myocardial HDAC6 perturbation has a deteriorative effect on the heart, and inhibition of HDAC6 can be a promising approach to alleviate CKD-induced myocardial remodeling.

Exosomes derived from TNF-α-treated bone marrow mesenchymal stem cells ameliorate myocardial infarction injury in mice

ABSTRACT Exosomes derived from bone marrow mesenchymal stem cells (BMSCs) exhibit considerable therapeutic potential for myocardial regeneration. In our investigation, we delved into their impact on various aspects of myocardial infarction (MI), including cardiac function, tissue damage, inflammation, and macrophage polarization in a murine model. We meticulously isolated the exosomes from TNF-α-treated BMSCs and evaluated their therapeutic efficacy in a mouse MI model induced by coronary artery ligation surgery. Our comprehensive analysis, incorporating ultrasound, serum assessment, Western blot, and qRT-PCR, revealed that exosomes from TNF-α-treated BMSCs demonstrated significant therapeutic potential in reducing MI-induced injury. Treatment with these exosomes resulted in improved cardiac function, reduced infarct area, and increased left ventricular wall thickness in MI mice. On a mechanistic level, exosome treatment fostered M2 macrophage polarization while concurrently suppressing M1 polarization. Hence, exosomes derived from TNF-α-treated BMSCs emerge as a promising therapeutic strategy for alleviating MI injury in a mouse model.

Decreased plasma ELABELA level as a novel screening indicator for heart failure: a cohort and observational study.

The predictive power of B-type natriuretic peptide (BNP) and left ventricular ejection fraction (LVEF) is limited by its low specificity in patients with heart failure (HF). Discovery of more novel biomarkers for HF better diagnosis is necessary and urgent. ELABELA, an early endogenous ligand for the G protein-coupled receptor APJ (Apelin peptide jejunum, Apelin receptor), exhibits cardioprotective actions. However, the relationship between plasma ELABELA and cardiac function in HF patients is unclear. To evaluate plasma ELABELA level and its diagnostic value in HF patients, a total of 335 patients with or without HF were recruited for our monocentric observational study. Plasma ELABELA and Apelin levels were detected by immunoassay in all patients. Spearman correlation analysis was used to analyze the correlation between plasma ELABELA or Apelin levels and study variables. The receiver operating characteristic curves were used to access the predictive power of plasma ELABELA or Apelin levels. Plasma ELABELA levels were lower, while plasma Apelin levels were higher in HF patients than in non-HF patients. Plasma ELABELA levels were gradually decreased with increasing New York Heart Association grade or decreasing LVEF. Plasma ELABELA levels were negatively correlated with BNP, left atrial diameter, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, and left ventricular posterior wall thickness and positively correlated with LVEF in HF patients. In contrast, the correlation between plasma Apelin levels and these parameters is utterly opposite to ELABELA. The diagnostic value of ELABELA, Apelin, and LVEF for all HF patients was 0.835, 0.673, and 0.612; the sensitivity was 62.52, 66.20, and 32.97%; and the specificity was 95.92, 67.23, and 87.49%, respectively. All these parameters in HF patients with preserved ejection fraction were comparable to those in total HF patients. Overall, plasma ELABELA levels were significantly reduced and negatively correlated with cardiac function in HF patients. Decreased plasma ELABELA levels may function as a novel screening biomarker for HF. A combined assessment of BNP and ELABELA may be a good choice to increase the accuracy of the diagnosis of HF.

PREVALENCE OF WILD–TYPE TRANSTHYRETIN CARDIAC AMYLOIDOSIS IN ELDERLY SUBJECTS FROM THE GENERAL POPULATION

Abstract Background Wild–type transthyretin cardiac amyloidosis (ATTRwt–CA) affects older adults, and is currently considered as a rare disorder. Objective We investigated for the first time the prevalence of ATTRwt–CA in elderly individuals from the general population. Methods General practitioners from Pisa, Italy, proposed a screening for ATTRwt–CA to all their patients aged 65–90 years, until 1,000 accepted. The following red flags were searched: interventricular septal thickness ≥12 mm, any echocardiographic, ECG or clinical hallmark of CA, or high sensitivity–troponin T ≥14 ng/L. Individuals with at least one red flag (n=346) were asked to undergo the search for a monoclonal protein and bone scintigraphy, and 216 accepted. Results Four patients received a non–invasive diagnosis of ATTRwt–CA. All complained of dyspnoea on moderate effort. A woman and a man aged 79 and 85 years, respectively, showed an intense cardiac tracer uptake (grade 3), left ventricular (LV) wall thickening, grade 2 to 3 diastolic dysfunction, and N–terminal pro–B–type natriuretic peptide (NT–proBNP) >1,000 ng/L. Two other patients (a man aged 74 years and a woman aged 83 years) showed a grade 2 uptake, an increased LV septal thickness, but preserved diastolic function, and NT–proBNP <300 ng/L. The prevalence of ATTR–CA in subjects ≥65 years was calculated as 0.46% (i.e., 4 out of the 870 subjects completing the screening, namely 654 not meeting the criteria for Step 2 and 216 progressing to Step 2). Conclusions ATTRwt–CA has a prevalence of 0.46% in elderly subjects from the general population.

Cardiac amyloidosis is not a single disease: a multiparametric comparison between the light chain and transthyretin forms.

Systemic amyloidosis represents a heterogeneous group of diseases resulting from amyloid fibre deposition. The purpose of this study is to establish a differential diagnosis algorithm targeted towards the two most frequent subtypes of CA. We prospectively included all consecutive patients with ATTR and AL evaluated between 2018 and 2022 in two centres in a score derivation cohort and a different validation sample. All patients had a complete clinical, biomarker, electrocardiographic, and imaging evaluation. Confirmation of the final diagnosis with amyloid typing was performed according to the current international recommendations. The study population included 81 patients divided into two groups: ATTR (group 1, n=32: 28 variant and 4 wild type) and AL (group 2, n=49). ATTR patients were younger (50.7±13.9 vs. 60.2±7.3years, P=0.0001), and significantly different in terms of NT-proBNP [ATTR: 1472.5ng/L (97-4218.5) vs. AL 8024ng/L (3058-14069) P=0.001], hs-cTn I [ATTR: 10ng/L (4-20) vs. AL 78ng/L (32-240), P=0.0002], GFR [ATTR 95.4mL/min (73.8-105.3) vs. AL: 68.4mL/min (47.8-87.4) P=0.003]. At similar left ventricular (LV) wall thickness and ejection fraction, the ATTR group had less frequently pericardial effusion (ATTR: 15% vs. AL: 33% P=0.0027), better LV global longitudinal strain (ATTR: -13.1%±3.5 vs. AL: -9.1%±4.3 P=0.04), RV strain (ATTR: -21.9%±6.2 vs. AL: -16.8%±6 P=0.03) and better reservoir function of the LA strain (ATTR: 22%±12 vs. AL: 13.6%±7.8 P=0.02). Cut-off points were calculated based on the Youden method. We attributed to 2 points for parameters having an AUC>0.75 (NT-proBNP AUC 0.799; hs-cTnI AUC 0.87) and 1 point for GFR (AUC 0.749) and TTE parameters (GLS AUC 0.666; RV FWS AUC 0.649, LASr AUC 0.643). A score of equal or more than 4 points has been able to differentiate between AL and ATTR (sensitivity 80%, specificity 62%, AUC=0.798). The differential diagnosis score system was applied to the validation cohort of 52 CA patients showing a sensitivity of 81% with specificity of 77%. CA is a complex entity and requires extensive testing for a positive diagnosis. This study highlights a series of non-invasive checkpoints, which can be useful in guiding the decision-making process towards a more accurate and rapid differential diagnosis.

MyoFold: Joint myocardial tissue composition and wall motion quantification via a highly folded sequence.

This study aims to develop and evaluate a novel cardiovascular MR sequence, MyoFold, designed for the simultaneous quantifications of myocardial tissue composition and wall motion. MyoFold is designed as a 2D single breathing-holding sequence, integrating joint T1/T2 mapping and cine imaging. The sequence uses a 2-fold accelerated balanced SSFP (bSSFP) for data readout and incorporates electrocardiogram synchronization to align with the cardiac cycle. MyoFold initially acquires six single-shot inversion-recovery images, completed during the diastole of six successive heartbeats. T2 preparation (T2-prep) is applied to introduce T2 weightings for the last three images. Subsequently, over the following six heartbeats, segmented bSSFP is performed for the movie of the entire cardiac cycle, synchronized with an electrocardiogram. A neural network trained using numerical simulations of MyoFold is used for T1 and T2 calculations. MyoFold was validated through phantom and in vivo experiments, with comparisons made against MOLLI, SASHA, T2-prep bSSFP, and the conventional cine. In phantom studies, MyoFold exhibited a 10% overestimation in T1 measurements, whereas T2 measurements demonstrated high accuracy. In vivo experiments revealed that MyoFold T1 had comparable accuracy to SASHA and precision similar to MOLLI. MyoFold demonstrated good agreement with T2-prep bSSFP in myocardial T2 measurements. No significant differences were observed in the quantification of left-ventricle wall thickness and function between MyoFold and the conventional cine. MyoFold presents as a rapid, simple, and multitasking approach for quantitative cardiovascular MR examinations, offering simultaneous assessment of tissue composition and wall motion. The sequence's multitasking capabilities make it a promising tool for comprehensive cardiac evaluations in clinical settings.

A case report of ATTR-amyloidosis following cardiac transplantation: thick ventricles that look alike

Abstract Background Transthyretin (ATTR-) amyloidosis is more prevalent than initially thought. As much as 13% of patients hospitalized with HFpEF may have ATTR-cardiomyopathy (CM). Conversely, heart transplant patients may manifest left ventricular hypertrophy or diastolic dysfunction, especially late after transplantation. Case Summary We present a case of a 82-year old male heart transplant patient, 31 years following orthotopic heart transplantation. While he was satisfied with his exercise capacity as an octogenarian, several years before he required pacemaker implantation due to 3rd degree AV block, had bilateral carpal tunnel syndrome treated with carpal tunnel release surgery and experienced idiopathic sudden deafness. Based on increasing left ventricular wall thickness during routine follow-up, a diagnosis of ATTR-amyloidosis was suspected. Ultimately, the diagnosis was confirmed non-invasively with a specific scintigraphic exam, while an additional physicochemical stain on an endomyocardial biopsy taken several years before provided pathological proof. We initiated tafamidis, yet stopped this treatment after one month because of gastro-intestinal intolerance. Ultimately, our patient died two years later due to heart failure. Discussion Our case shows the long delay between the onset of transthyretin deposition, the presence of clinical signs and the final diagnosis. Echocardiographic findings suggestive for ATTR-CM include left ventricular hypertrophy and diastolic dysfunction, which are both common in heart transplant patients. Yet, ATTR-CM should be considered in the differential diagnosis, especially late after transplantation, in this closely monitored population.

Echocardiographic manifestations of mitochondrial disease with GTPBP3 gene mutations: A case report.

Mitochondrial diseases are a group of disorders in which mutations in mitochondrial DNA or nuclear DNA lead to dysfunctional oxidative phosphorylation of cells, with mutations in mitochondrial DNA being the most common cause of mitochondrial disease, and mutations in nuclear genes being rarely reported. The echocardiographic findings of mitochondrial diseases with nuclear gene mutations in children's hearts are even rarer. Even more valuable is that we followed up the patient for 4 years and dynamically observed the cardiac echocardiographic manifestations of mitochondrial disease. Provide ideas for the clinical diagnosis and prognosis of mitochondrial diseases. The patient was seen in the pediatric outpatient clinic for poor strength and mental retardation. echocardiography: mild left ventricular (LV) enlargement and LV wall thickening. Nuclear genetic testing: uanosine triphosphate binding protein 3 (GTPBP3) gene mutation. Diagnosis of mitochondrial disease. Mitochondrial disease with GTPBP3 gene mutations. After receiving drug treatment, the patient exhibited a reduction in lactate levels, an enhanced physical condition compared to prior assessments, and demonstrated average intellectual development. For echocardiographic indications of LV wall thickening and LV enlargement, one needs to be alert to the possibility of hereditary cardiomyopathy, especially in children.

Withaferin A as a Potential Therapeutic Target for the Treatment of Angiotensin II-Induced Cardiac Cachexia.

In our previous studies, we showed that the generation of ovarian tumors in NSG mice (immune-compromised) resulted in the induction of muscle and cardiac cachexia, and treatment with withaferin A (WFA; a steroidal lactone) attenuated both muscle and cardiac cachexia. However, our studies could not address if these restorations by WFA were mediated by its anti-tumorigenic properties that might, in turn, reduce the tumor burden or WFA's direct, inherent anti-cachectic properties. To address this important issue, in our present study, we used a cachectic model induced by the continuous infusion of Ang II by implanting osmotic pumps in immunocompetent C57BL/6 mice. The continuous infusion of Ang II resulted in the loss of the normal functions of the left ventricle (LV) (both systolic and diastolic), including a significant reduction in fractional shortening, an increase in heart weight and LV wall thickness, and the development of cardiac hypertrophy. The infusion of Ang II also resulted in the development of cardiac fibrosis, and significant increases in the expression levels of genes (ANP, BNP, and MHCβ) associated with cardiac hypertrophy and the chemical staining of the collagen abundance as an indication of fibrosis. In addition, Ang II caused a significant increase in expression levels of inflammatory cytokines (IL-6, IL-17, MIP-2, and IFNγ), NLRP3 inflammasomes, AT1 receptor, and a decrease in AT2 receptor. Treatment with WFA rescued the LV functions and heart hypertrophy and fibrosis. Our results demonstrated, for the first time, that, while WFA has anti-tumorigenic properties, it also ameliorates the cardiac dysfunction induced by Ang II, suggesting that it could be an anticachectic agent that induces direct effects on cardiac muscles.

DETERMINANTS OF ADULT CARDIAC STRUCTURE: DEVELOPMENTAL INFLUENCE OF PHYSICAL ACTIVITY, SYSTOLIC BLOOD PRESSURE AND TV WATCHING

INTRODUCTION The impacts of health-related behaviours and risk factor exposures across childhood and adolescence on the adult heart are largely unexplored. We investigated whether early-life trajectories for physical activity (PA), sedentary behaviour and systolic blood pressure (SBP) are associated with cardiac structure in adulthood. METHODS Data collected throughout childhood and adolescence on PA, TV watching and SBP in a cohort study were used to develop antecedent trajectories. At age ∼29yrs, participants were invited to undergo an echocardiogram, to assess left ventricular mass (LVM), LV internal diameter (LVID) and LV wall thickness (LVWT). Analysis was performed between trajectories, separately by sex. RESULTS 723 participants were included. In males, LVM was greater in the antecedent High-PA trajectory (184.1±35.6g), compared to both Mid-PA (171.7±36.1g, P=0.014) and Low-PA (166.7±38.0g, P=0.021). This was related to greater LVID in High-PA compared to both Mid-PA (Δ1.3±0.5cm, P=0.018) and Low-PA (Δ1.3±0.8cm, P=0.087) groups; there were no differences in LVWT (all P>0.050). No differences were found in heart structure between PA trajectory groups in females (all P>0.050). For antecedent SBP, LVM was lower in both the Low-SBP (155.7±30.5g) and Normal-SBP groups (172.9±36.7g) compared to both High-normal (184.8±32.9g) and High-SBP (206.2±41.3g) in males (all P<0.001). This was primarily driven by larger LVWT in High-normal (Δ1.2±0.2g, P=0.001) and High-SBP groups (1.9±0.5g, P=0.001); no differences were observed for LVID (P=0.398). These findings for SBP were similar in females, with the highest SBP group having the greatest LVM and LVWT (all P<0.001). There were no significant impacts of antecedent TV trajectories on adult cardiac measures (all P>0.050). CONCLUSION Higher developmental SBP is associated with larger heart size and wall thickness in adulthood. Higher developmental PA levels are associated with larger cardiac chamber dimension in adult males, but not females. These findings suggest adult cardiac structure may be influenced by early-life risk factor exposures.

Evaluation of left ventricular function in normotensive type-2 dm patients by echocardiography

The prevalence of diabetes mellitus (DM) is increasing globally. Indians are also believed to have a greater degree of insulin resistance and a stronger genetic predisposition to diabetes. Type II DM is a risk factor for cardiovascular disease and cardiovascular complications and these are a major cause of mortality and morbidity in diabetic patients. Left ventricular dysfunction, increased left ventricular wall thickness, increased left ventricular mass, and specific diabetic cardiomyopathy are some of the cardiovascular complications associated with diabetes. So the present study was performed to assess normotensive diabetic patients by echocardiography to evaluate their left ventricular function. A case control cross sectional study was conducted on 40 normotensive type 2 diabetes mellitus patients. 40 patients who were non-diabetic, non-hypertensive were taken as a control. A standard 2D echocardiography with M mode and Doppler was performed on case and control. In our study among 40 cases, 55% were male and 45% were female with mean age of case population being 47.5±7.24 year and among 40 controls, 50% were male and 50% were female with mean age 48.03±7.14 year. Mean BMI in case group was 29.49±2.37 kg/m2 and in control group 29.36±2.46 kg/m2. In our study we found that LVDD was present in 57.5% cases, 47.5% of cases had grade 1 LVDD whereas 10% had grade 2 LVDD. In comparison, only 10% of controls had LVDD with all of them having grade 1 LVDD. Also LV Systolic dysfunction, LVM and LVMI were higher in cases as compared to controls. Thus we concluded that the prevalence of left ventricular diastolic dysfunction in asymptomatic, normotensive patients with type 2 DM without significant coronary artery disease is much higher than previously suspected as evidenced by the results of this study and also of similar other studies and it increases with the duration of Diabetes. Left ventricular systolic dysfunction, LVM and LVMH prevalence were also higher in cases as compared to controls and they also correlate with duration of Diabetes.

Moderate Endurance Exercise Increases Arrhythmia Susceptibility and Modulates Cardiac Structure and Function in a Sexually Dimorphic Manner.

Although moderate endurance exercise has been reported to improve cardiovascular health, its effects on cardiac structure and function are not fully characterized, especially with respect to sexual dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice. C57BL/6J mice of both sexes were run on a treadmill for 6 weeks. ECG and echocardiography were performed every 2 weeks. After 6 weeks of exercise, mice were euthanized, and triple parametric optical mapping was performed on Langendorff perfused hearts to assess cardiac electrophysiology. Arrhythmia inducibility was tested by programmed electrical stimulation. Left ventricular tissue was fixed, and RNA sequencing was performed to determine exercise-induced transcriptional changes. Exercise-induced left ventricular dilatation was observed in female mice alone, as evidenced by increased left ventricular diameter and reduced left ventricular wall thickness. Increased cardiac output was also observed in female exercised mice but not males. Optical mapping revealed further sexual dimorphism in exercise-induced modulation of cardiac electrophysiology. In female mice, exercise prolonged action potential duration and reduced voltage-calcium influx delay. In male mice, exercise reduced the calcium decay constant, suggesting faster calcium reuptake. Exercise increased arrhythmia inducibility in both male and female mice; however, arrhythmia duration was increased only in females. Lastly, exercise-induced transcriptional changes were sex dependent: females and males exhibited the most significant changes in contractile versus metabolism-related genes, respectively. Our data suggest that moderate endurance exercise can significantly alter multiple aspects of cardiac physiology in a sex-dependent manner. Although some of these effects are beneficial, like improved cardiac mechanical function, others are potentially proarrhythmic.

Frequency of misdiagnosis in hypertrophic cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is characterized by unexplained left ventricle hypertrophy (LVH) ≥15mm. The condition is often hereditary and family screening is recommended to reduce the risk of adverse disease complications and premature death among relatives. Correct diagnosis of index patients is important to ensure that only relatives at risk of disease development are invited for family screening. To investigate if patients with ICD-10 codes for HCM (DI421) or hypertrophic obstructive cardiomyopathy (DI422) fulfilled recognised diagnostic criteria. All patients with ICD-10 codes for HCM or HOCM at a Department of Cardiology were identified and had their diagnosis validated by a cardiac investigation or a review of their medical records and previous investigations. Two hundred and forty patients had ICD-10 codes for HCM/HOCM, of whom 202 (84%, 202/240) underwent re-examination, while 38 (16%, 38/240) had their hospital notes reviewed. Seventy-six patients (32%, n=76/240) did not fulfil diagnostic criteria, of whom 39, (51%, n=39/76) had normal (10mm) or modest LV wall thickness (11-14mm). The remaining 37 patients (49%, n=37/76) had LVH ≥15mm, which was well-explained by uncontrolled hypertension, (32%, n=24/76), aortic valve stenosis (19%, n=7/76) or wild-type amyloidosis (16%, 6/76). One-third of patients with ICD-10 codes for HCM or HOCM did not fulfil recognised diagnostic criteria. Incorrect diagnosis of HCM may cause unnecessary family investigations which may be associated with anxiety, and a waste of health care resources. This highlights the need for specialised cardiomyopathy services to ensure correct diagnosis and management of HCM.

The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats

BackgroundIn people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight.ResultsAt baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17–29%), with a median reduction in body fat mass of 45% (26–64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction.ConclusionAn increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.

Detraining among Athletes-Is Withdrawal of Adaptive Cardiovascular Changes a Hint for the Differential Diagnosis of Physically Active People?

An athlete's training aims to achieve the highest possible sports results by improving physical dispositions which lead to cardiac adaptive changes. The annual training cycle is divided into periods. The preparatory period begins with gradually increasing training intensity and volume until the competitive period occurs, when the athlete's maximum performance is expected. Finally, the athlete enters a phase of loss of fitness, which is called detraining. Detraining is a time of resting both physically and mentally from the training regime and usually lasts about 4 weeks for endurance athletes. We collected data from much research on athletes' detraining. According to these data, the earliest change after detraining seems to be a decrease in left ventricular wall thickness and left ventricular mass, followed by decreased performance parameters, diastolic diameter of the left ventricle and size of the left atrium. A reversal of adaptive changes affects the left heart chamber first, then the right atrium and, finally, the right ventricle. Training reduction is often proposed as a method of differentiating an athlete's heart from cardiomyopathies. The aim of this study is to consider the diagnostic value of detraining in differentiating athletes' hearts from cardiomyopathies. We suggest that detraining cannot be conclusive in differentiating the disease from adaptive changes. Although a withdrawal of the characteristic morphological, functional and electrocardiographic changes occurs in healthy athletes during detraining, it can also concern individuals with cardiomyopathies due to the lower expression of abnormal features after decreased training loads. Therefore, a quick diagnosis and individual assessments using imaging and genetic tests are essential to recommend a proper type of activity.

Reported physical symptoms during screening echocardiography are not associated with presence of suspected hypertrophic cardiomyopathy.

The prevalence of hypertrophic cardiomyopathy (HCM) can be silent and can present with sudden death as the first manifestation of this disease. The goal of this study was to evaluate any association between reported physical symptoms with the presence of suspected HCM. The Anthony Bates Foundation has been performing screening echocardiography across the United States for the prevention of sudden death since 2001. A total of 4,120 subjects between the ages of 6 and 79 underwent echocardiographic screening. We evaluated any association between any symptoms and suspected HCM defined as any left ventricular wall thickness ³ 15 mm. The total prevalence of suspected HCM in the entire study population was 1.1%. The presence of physical symptoms was not associated with HCM (chest pain in 4.3% of participants with HCM vs. 9.9% of the control, p=0.19, palpitation in 4.3% of participants with HCM vs. 7.3% of the control., p=0.41, shortness of breath in 6.4% of participant with HCM vs. 11.7% of the control., p=0.26, lightheadedness in 4.3% of participant with HCM vs. 13.1% of the control., p=0.07, ankle swelling in 2.1% of participant with HCM vs. 4.0% of the control., p=0.52, dizziness in 8.5% of participant with HCM vs. 12.2% of the control., p=0.44). Echocardiographic presence of suspected HCM is not associated with a higher prevalence of physical symptoms in the participants undergoing screening echocardiography.

Voluntary Wheel Running Reduces Cardiometabolic Risks in Female Offspring Exposed to Lifelong High-Fat, High-Sucrose Diet.

Maternal and postnatal overnutrition has been linked to an increased risk of cardiometabolic diseases in offspring. This study investigated the impact of adult-onset voluntary wheel running to counteract cardiometabolic risks in female offspring exposed to a life-long high-fat, high-sucrose (HFHS) diet. Dams were fed either a HFHS or a low-fat, low-sucrose (LFLS) diet starting from 8 weeks prior to pregnancy and continuing throughout gestation and lactation. Offspring followed their mothers' diets. At 15 weeks of age, they were divided into sedentary (Sed) or voluntary wheel running (Ex) groups, resulting in four groups: LFLS/Sed (n = 10), LFLS/Ex (n = 5), HFHS/Sed (n = 6), HFHS/Ex (n = 5). Cardiac function was assessed at 25 weeks, with tissue collection at 26 weeks for mitochondrial respiratory function and protein analysis. Data were analyzed using two-way ANOVA. While maternal HFHS diet did not affect the offspring's body weight at weaning, continuous HFHS feeding post-weaning resulted in increased body weight and adiposity, irrespective of the exercise regimen. HFHS/Sed offspring showed increased left ventricular wall thickness and elevated expression of enzymes involved in fatty acid transport (CD36, FABP3), lipogenesis (DGAT), glucose transport (GLUT4), oxidative stress (protein carbonyls, nitrotyrosine), and early senescence markers (p16, p21). Their cardiac mitochondria displayed lower oxidative phosphorylation (OXPHOS) efficiency and reduced expression of OXPHOS complexes and fatty acid metabolism enzymes (ACSL5, CPT1B). However, HFHS/Ex offspring mitigated these effects, aligning more with LFLS/Sed offspring. Adult-onset voluntary wheel running effectively counteracts the detrimental cardiac effects of a lifelong HFHS diet, improving mitochondrial efficiency, reducing oxidative stress, and preventing early senescence. This underscores the significant role of physical activity in mitigating diet-induced cardiometabolic risks.

Long-Term Clinical-Pathologic Results of Enzyme Replacement Therapy in Prehypertrophic Fabry Disease Cardiomyopathy.

The limited ability of enzyme replacement therapy (ERT) in removing globotriaosylceramide from cardiomyocytes is recognized for advanced Fabry disease cardiomyopathy (FDCM). Prehypertrophic FDCM is believed to be cured or stabilized by ERT. However, no pathologic confirmation is available. We report here on the long-term clinical-pathologic impact of ERT on prehypertrophic FDCM. Fifteen patients with Fabry disease with left ventricular maximal wall thickness ≤10.5 mm at cardiac magnetic resonance required endomyocardial biopsy because of angina and ventricular arrhythmias. Endomyocardial biopsy showed coronary small-vessel disease in the angina cohort, and vacuoles in smooth muscle cells and cardiomyocytes ≈20% of the cell surface containing myelin bodies at electron microscopy. Patients received α-agalsidase in 8 cases, and β-agalsidase in 7 cases. Both groups experienced symptom improvement except 1 patients treated with α-agalsidase and 1 treated with β-agalsidase. After ERT administration ranging from 4 to 20 years, all patients had control cardiac magnetic resonance and left ventricular endomyocardial biopsy because of persistence of symptoms or patient inquiry on disease resolution. In 13 asymptomatic patients with FDCM, left ventricular maximal wall thickness and left ventricular mass, cardiomyocyte diameter, vacuole surface/cell surface ratio, and vessels remained unchanged or minimally increased (left ventricular mass increased by <2%) even after 20 years of observation, and storage material was still present at electron microscopy. In 2 symptomatic patients, FDCM progressed, with larger and more engulfed by globotriaosylceramide myocytes being associated with myocardial virus-negative lymphocytic inflammation. ERT stabilizes storage deposits and myocyte dimensions in 87% of patients with prehypertrophic FDCM. Globotriaosylceramide is never completely removed even after long-term treatment. Immune-mediated myocardial inflammation can overlap, limiting ERT activity.

Multinational experience with next-generation sequencing: opportunity to identify transthyretin cardiac amyloidosis and Fabry disease.

Sarcomeric hypertrophic cardiomyopathy (HCM) must be differentiated from phenotypically similar conditions because clinical management and prognosis may greatly differ. Patients with unexplained left ventricular hypertrophy require an early, confirmed genetic diagnosis through diagnostic or predictive genetic testing. We tested the feasibility and practicality of the application of a 17-gene next-generation sequencing (NGS) panel to detect the most common genetic causes of HCM and HCM phenocopies, including treatable phenocopies, and report detection rates. Identification of transthyretin cardiac amyloidosis (ATTR-CA) and Fabry disease (FD) is essential because of the availability of disease-specific therapy. Early initiation of these treatments may lead to better clinical outcomes. In this international, multicenter, cross-sectional pilot study, peripheral dried blood spot samples from patients of cardiology clinics with an unexplained increased left ventricular wall thickness (LVWT) of ≥13 mm in one or more left ventricular myocardial segments (measured by imaging methods) were analyzed at a central laboratory. NGS included the detection of known splice regions and flanking regions of 17 genes using the Illumina NextSeq 500 and NovaSeq 6000 sequencing systems. Samples for NGS screening were collected between May 2019 and October 2020 at cardiology clinics in Colombia, Brazil, Mexico, Turkey, Israel, and Saudi Arabia. Out of 535 samples, 128 (23.9%) samples tested positive for pathogenic/likely pathogenic genetic variants associated with HCM or HCM phenocopies with double pathogenic/likely pathogenic variants detected in four samples. Among the 132 (24.7%) detected variants, 115 (21.5%) variants were associated with HCM and 17 (3.2%) variants with HCM phenocopies. Variants in MYH7 (n=60, 11.2%) and MYBPC3 (n=41, 7.7%) were the most common HCM variants. The HCM phenocopy variants included variants in the TTR (n=7, 1.3%) and GLA (n=2, 0.4%) genes. The mean (standard deviation) ages of patients with HCM or HCM phenocopy variants, including TTR and GLA variants, were 42.8 (17.9), 54.6 (17.0), and 69.0 (1.4) years, respectively. The overall diagnostic yield of 24.7% indicates that the screening strategy effectively identified the most common forms of HCM and HCM phenocopies among geographically dispersed patients. The results underscore the importance of including ATTR-CA (TTR variants) and FD (GLA variants), which are treatable disorders, in the differential diagnosis of patients with increased LVWT of unknown etiology.

A Murine Model of Hyperlipidemia-Induced Heart Failure with Preserved Ejection Fraction.

The pathophysiology of heart failure with preserved ejection fraction (HFpEF) driven by lipotoxicity is incompletely understood. Given the urgent need for animal models that accurately mimic cardio-metabolic HFpEF, a hyperlipidemia-induced murine model was developed by reverse engineering phenotypes seen in HFpEF patients. This model aimed to investigate HFpEF, focusing on the interplay between lipotoxicity and metabolic syndrome. Hyperlipidemia was induced in wild-type (WT) mice on a 129J strain background through bi-weekly intraperitoneal injections of poloxamer-407 (P-407), a block co-polymer that blocks lipoprotein lipase, combined with a single intravenous injection of adeno-associated virus 9-cardiac troponin T-low-density lipoprotein receptor (AAV9-cTnT-LDLR). Extensive assessments were conducted between 4 and 8 weeks post-treatment, including echocardiography, blood pressure recording, whole-body plethysmography, echocardiography (ECG) telemetry, activity wheel monitoring (AWM), and biochemical and histological analyses. The LDLR/P-407 mice exhibited distinctive features at four weeks, including diastolic dysfunction, preserved ejection fraction, and increased left ventricular wall thickness. Notably, blood pressure and renal function remained within normal ranges. Additionally, ECG and AWM revealed heart blocks and reduced activity, respectively. Diastolic function deteriorated at eight weeks, accompanied by a significant decline in respiratory rates. Further investigation into the double treatment model revealed elevated fibrosis, wet/dry lung ratios, and heart weight/body weight ratios. The LDLR/P-407 mice exhibited xanthelasmas, ascites, and cardiac ischemia. Interestingly, sudden deaths occurred between 6 and 12 weeks post-treatment. The murine HFpEF model offers a valuable and promising experimental resource for elucidating the intricacies of metabolic syndrome contributing to diastolic dysfunction within the context of lipotoxicity-mediated HFpEF.